Recent research has suggested that increasing levels of physical activity are associated with a reduction in the independent components that contribute to total energy expenditure (such as resting metabolic rate and non-exercise movement) - this occurs to conserve energy required for physical activity where energy provision becomes scarce. There are potential deleterious health and performance consequences of a reduced energy supply to fundamental metabolic processes, putting individuals regularly undertaking high levels of physical activity, such as endurance athletes, at risk. However, this association is largely based on observational data in only moderately active populations, and it is currently unclear what role energy balance status and biological sex has on this relationship. This research intends to address these unknowns by assessing the impact of diet-induced manipulation of energy balance (conditions of energy deficit and energy surplus) in individuals undertaking habitually high levels of physical activity on independent components of total energy expenditure (resting metabolism, exercise and non-exercise movement). Male and female athletes conducting regular moderate-to-high training volumes will undertake a randomised crossover study with a 7-day state of energy deficit and a 7-day state of energy surplus. Participants will continue to live and train as normal, but their diet will be controlled by specific food provision over the intervention periods in order to facilitate both conditions. Independent components of energy expenditure, markers of health, metabolism and performance will be measured to allow for comparison of conditions.
People with very active lifestyles such as athletes, dancers, and military personnel, need to eat a lot of food to make up for the large amount of energy they burn. If they don't match their food intake to their energy needs, they may enter a state of 'energy deficit'. This means their bodies are burning more calories than they're taking in, which can lower performance, increase the risk of injuries and illnesses, and potentially harm overall health. Traditional scientific understanding assumes that more doing physically activity leads to burning more calories (the 'additive' model). However, newer studies suggest that the body might have built-in safeguards to limit how many total calories it burns, no matter how much a person exercises. This idea (the 'constrained' model) proposes that when people exercise more, their bodies might compensate by slowing down other metabolic processes to keep overall energy use within a certain range. Although this mechanism could help the body conserve energy, it may also mean that essential functions (like immune system support and reproductive function) can become impaired. Most research on energy deficit so far has focused on people with normal or moderate levels of physical activity. Because extremely active people experience far higher daily energy demands, the 'constrained' mechanisms could manifest differently or to a greater degree and the negative health and performance consequences might be more severe. There is also limited knowledge about how quickly these changes in energy use begin and how they affect important processes at the cellular level, such as muscle mitochondrial function or immune cell health. This study aims to fill these gaps by measuring total energy use (and its separate parts) in highly active individuals under two conditions: when participants eat enough to cover their energy demands and when participants are purposely in an energy deficit (intentionally eating less than they need). One of our main goals is to measure changes in resting metabolic rate (RMR), which is the energy the body uses at rest to keep vital functions going. Investigators will also examine cellular changes by looking at indicators like immune cell function to see how these might help us detect early signs of harmful energy shortages. By understanding whether, and to what extent, the body's energy use is 'constrained', investigators can develop better guidelines to help very active individuals avoid unhealthy energy deficits. Ultimately, this research could improve both performance and long-term health for athletes, military personnel, dancers, and anyone else who regularly exercises at high levels.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
20
Participants receive a prepared diet providing approximately 50% of their estimated daily energy expenditure to induce a sustained energy deficit
Participants continue their normal diet with the addition of high-calorie snack items to achieve an approximate daily energy surplus
University of Bath
Bath, United Kingdom
Resting metabolic rate (RMR) in kcal/day
The effect of a 7-day period of energy expenditure-matched diet-induced energy deficit versus energy surplus on RMR. Measured via indirect calorimetry using the Douglas bag method. Expired gas will be collected in a seated, fasted state under thermoneutral conditions, and oxygen consumption and carbon dioxide production will be used to calculate energy expenditure.
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Total energy expenditure (from doubly labelled water) in kcal/day
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.
Total energy expenditure ( from sum of independent components of energy expenditure) in kcal/day
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9
Peripheral blood mononuclear cell (PBMC) mitochondrial respiration
Assessment of mitochondrial respiratory function in isolated PBMCs using high-resolution respirometry (Oroboros). Measures include basal (routine), leak, oxidative phosphorylation (OXPHOS), and electron transfer system (ETS) capacity states. Data will be used to assess changes in mitochondrial function in response to exercise and nutritional intervention. Units: pmol O₂·s-¹·10⁶ cells-¹ (picomoles of oxygen consumed per second per million PBMCs).
Time frame: Measured pre- and post-exercise at visits 2/3 (pre- and post-intervention 1) and visits 4/5 (pre- and post-intervention 2), approximately weeks 4-12.
Sub-maximal exercise performance (during steady-state treadmill exercise)
Running economy (oxygen consumption at a fixed submaximal speed, expressed as ml O₂·kg-¹·min-¹)
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Free T3 in pmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks.
Interstitial glucose concentration in mmol/l
Continuous glucose monitoring using Dexcom G7 reporting mean daily and daily variability in interstitial glucose concentration.
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.
Bone mineral density (DEXA)
Bone mineral density will be assessed using dual-energy X-ray absorptiometry (DEXA). DEXA will provide areal BMD (g/cm²).
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Bone mineral density (pQCT)
Bone mineral density will be assessed using peripheral quantitative computed tomography (pQCT) at the tibia. Measures will include volumetric BMD (vBMD) in mg/cm³ in cortical and trabecular compartments.
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Subjective measures of fatigue
Daily subjective fatigue will be assessed using the Hooper Index (fatigue subscale, 5-item 1-5 Likert scale). Higher scores indicate greater perceived fatigue. Units: Hooper Index: total score (5-25)
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Sleep duration in h/night
Accelerometer-dervied using arm-worn Actigraph LEAP device.
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.
Non-exercise activity thermogenesis (NEAT) (estimated from ActiGraph LEAP device) in kcal/day
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9
Exercise energy expenditure (estimated from ActiGraph LEAP device) in kcal/day
Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9
Sub-maximal exercise performance (during steady-state treadmill exercise)
Substrate utilisation (absolute in g·min-¹)
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Sub-maximal exercise performance (during steady-state treadmill exercise)
Substrate utilisation (relative as % total energy expenditure)
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Bone mineral density (pQCT)
Cross-sectional area in mm²
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Bone mineral density (pQCT)
Strength-strain index in mm³
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Subjective measures of fatigue
Daily subjective fatigue will be assessed using the Fatigue Assessment Scale (FAS), a 10-item validated questionnaire scored from 10 to 50. Higher scores indicate greater perceived fatigue. Units: total score (10-50).
Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Total testosterone in nmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Free testosterone in pg/mL
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
cortisol in nmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
IGF-1 in ng/mL
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
leptin in ng/mL
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: oestradiol in pmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: FSH in IU/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: LH in IU/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Inflammatory markers: interleukin-6 (IL-6) in pg/mL
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
high-sensitivity C-reactive protein (hsCRP) in mg/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
ferritin in µg/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
serum iron in µmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
transferrin in g/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
total iron binding capacity (TIBC) in µmol/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
transferrin saturation as a percentage
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
soluble transferrin receptor in mg/L
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
hepcidin in ng/mL
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Lipid markers: total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in mmol/L; non-esterified fatty acids (NEFA) in mmol/L; and glycerol in µmol/L.
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
HbA1c will be reported in both % (DCCT-aligned) and mmol/mol (IFCC standard).
Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
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